Tasigna News

Tasigna Q&A

WARNING: QT PROLONGATION AND SUDDEN DEATHS

Tasigna prolongs the QT interval (5.2). Sudden deaths have been reported in patients receiving nilotinib (5.3). Tasigna should not be used in patients with hypokalemia, hypomagnesemia, or long QT syndrome (4). Hypokalemia or hypomagnesemia must be corrected prior to Tasigna administration and should be periodically monitored (5.2). Drugs known to prolong the QT interval and strong CYP3A4 inhibitors should be avoided (5.7). Patients should avoid food 2 hours before and 1 hour after taking dose (5.8). Use with caution in patients with hepatic impairment (5.9). ECGs should be obtained to monitor the QTc at baseline, seven days after initiation, and periodically thereafter, as well as following any dose adjustments. (5.2, 5.3, 5.6, 5.12)

TASIGNA SUMMARY

Tasigna (nilotinib) belongs to a pharmacologic class of drugs known as kinase inhibitors.

Tasigna (nilotinib) is indicated for the treatment of chronic phase and accelerated phase Philadelphia chromosome positive chronic myelogenous leukemia (CML) in adult patients resistant or intolerant to prior therapy that included imatinib. The effectiveness of Tasigna is based on hematologic and cytogenetic response rates [ See Clinical Studies (14)]. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival.

Nilotinib: evaluation and analysis of its role in chronic myeloid leukemia. [2011.02]Nilotinib, formally known as AMN107, is a second-generation tyrosine kinase inhibitor, rationally designed from its revolutionary parent compound imatinib, to produce a 30-40-fold enhancement in the inhibition of the BCR-ABL1-derived oncoprotein associated with chronic myeloid leukemia... With the emergence of supportive trial data, it is likely to have a leading role both in the front-line management of newly presenting patients and in the second-line treatment of patients resistant to or intolerant of imatinib and other second-line agents.

Effects of nilotinib on single-dose warfarin pharmacokinetics and pharmacodynamics: a randomized, single-blind, two-period crossover study in healthy subjects. [2011]BACKGROUND AND OBJECTIVE: Nilotinib (Tasigna(R)), a highly selective and potent BCR-ABL tyrosine kinase inhibitor, is approved for the treatment of chronic myeloid leukaemia in the chronic phase (CML-CP) and the accelerated phase (CML-AP) in patients resistant or intolerant to prior therapy, including imatinib. Nilotinib has shown competitive inhibition of cytochrome P450 enzyme (CYP) 2C9 in vitro, but its effect on CYP2C9 activity in humans is unknown. This study evaluated the effects of nilotinib on the pharmacokinetics and pharmacodynamics of warfarin, a sensitive CYP2C9 substrate, in healthy subjects... CONCLUSION: The study results demonstrate that nilotinib has no effect on single-dose warfarin pharmacokinetics and pharmacodynamics. This implies that nilotinib is unlikely to inhibit CYP2C9 activity in human subjects. These findings suggest that warfarin and nilotinib may be used concurrently as needed.

Gleevec as Maintenance Therapy After Cytogenetic Response With Nilotinib in Newly Diagnosed Chronic Myelogenous Leukemia [Recruiting]
The results of the International Randomized Study of Interferon and STI571 (IRIS) trial
indicate that in patients with chronic phase CML treated with first line imatinib,
achievement of a complete or partial cytogenetic response (CCyR or PCyR) at 12 months is
associated with a significantly better progression-free survival (PFS).
Second generation tyrosine kinase inhibitors such as nilotinib can overcome imatinib
resistance because of greater potency to bind to BCR-ABL. Recent results indicate that, in
patients with previously untreated chronic phase CML, nilotinib results in a faster and
higher rate of CCyR or PCyR than imatinib. However, nilotinib use is associated with diet
restriction and much higher financial cost.
The primary objective of this study is to evaluate the ability of imatinib to maintain a
complete cytogenetic response (CcyR) in patients who achieved a CCyR after 12 months of
first-line treatment with nilotinib.